Genetic Variant CISD3:p.Pro10Leu (chr17-38730387-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001136498.2(CISD3):c.29C>T(p.Pro10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,205,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

CISD3
NM_001136498.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.43

Publications

1 publications found

Variant links:

Genes affected

CISD3 (HGNC:27578): (CDGSH iron sulfur domain 3) CISD3 is a member of the CDGSH domain-containing family, which may play a role in regulating electron transport and oxidative phosphorylation (Wiley et al., 2007 [PubMed 17376863]).[supplied by OMIM, Apr 2008]

CISD3 links:

ENSG00000275665 (HGNC:):

ENSG00000275665 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030017734).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136498.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CISD3	NM_001136498.2	MANE Select	c.29C>T	p.Pro10Leu	missense	Exon 1 of 4	NP_001129970.1	P0C7P0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CISD3	ENST00000613478.2	TSL:2 MANE Select	c.29C>T	p.Pro10Leu	missense	Exon 1 of 4	ENSP00000483781.1	P0C7P0
CISD3	ENST00000619858.1	TSL:1	n.29C>T		non_coding_transcript_exon	Exon 1 of 3
CISD3	ENST00000894448.1		c.29C>T	p.Pro10Leu	missense	Exon 1 of 4	ENSP00000564507.1

Frequencies

GnomAD3 genomes

AF:

0.000451

AC:

AN:

150732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000588

AC:

AN:

1054318

Hom.:

Cov.:

AF XY:

0.0000402

AC XY:

AN XY:

497584

show subpopulations

African (AFR)

AF:

0.00260

AC:

AN:

21906

American (AMR)

AF:

0.00

AC:

AN:

7462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13096

East Asian (EAS)

AF:

0.00

AC:

AN:

24300

South Asian (SAS)

AF:

0.00

AC:

AN:

19512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2764

European-Non Finnish (NFE)

AF:

0.00000111

AC:

AN:

903220

Other (OTH)

AF:

0.0000959

AC:

AN:

41708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000464

AC:

AN:

150840

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

AN XY:

73704

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

41392

American (AMR)

AF:

0.000132

AC:

AN:

15156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67554

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000604

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.7

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0010

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.044

M_CAP

Benign

0.032

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PhyloP100

-1.4

PrimateAI

Uncertain

0.57

Sift4G

Benign

0.12

Polyphen

0.064

Vest4

0.056

MutPred

0.35

Gain of helix (P = 0.0022)

MVP

0.11

ClinPred

0.049

GERP RS

-0.74

PromoterAI

-0.045

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.040

gMVP

0.32

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over